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Purpose: Cancer can be a source of significant psychological and physical stress. Prolonged stressful stimuli can influence the stress response, mediated by the hypothalamic–pituitary–adrenal (HPA) axis. However, there is limited literature investigating HPA axis function in patients with cancer. Methods: A systematic literature review of case–control studies was conducted comparing individuals with and without cancer examining the HPA axis function. Databases (MEDLINE, PubMed, Scopus) were searched from inception to May 2023. Results: Seventeen studies met eligibility criteria: nine unstimulated‐cortisol studies and eight reporting the effect of HPA stimulation or suppression. Sixteen studies reported altered levels of HPA function in cancer patients relative to controls, including 13 reporting increased baseline or hyperactive cortisol responses, and four—decreased baseline cortisol or blunted cortisol responses, two of which had patient groups with now known cortisol‐suppressing treatments. HPA dysfunction was observed in patients of both sexes, diverse ages, stages of cancer and cancer treatments. Six papers reported on clinical outcomes with cases experiencing higher levels of fatigue, stress, poor memory, poor well‐being and disturbed sleep. There was significant heterogeneity in methodologies across the studies. Conclusion: HPA dysfunction was common in patients with cancer relative to cancer‐free controls. The majority of studies in cancer reported an increased baseline cortisol and increased response to HPA stimulation. There is a need for well‐powered studies using standardised methodology examining the mechanisms of HPA dysregulation and their health outcomes, to enable the development of appropriate tools for the diagnosis and management of HPA dysfunction in cancer. This systematic review of 17 studies comparing HPA axis function in individuals with cancer as compared to controls suggests that HPA dysregulation is common in people with cancer. There was significant variability in methodologies used to measure HPA dysregulation, which limits the interpretation of findings, and few only studies examined the impact of HPA dysregulation on patient outcomes. There is a need for studies that use a standardised approach to HPA axis measurement and examine patient outcomes to determine its clinical impact. [ABSTRACT FROM AUTHOR]

Aims: To examine the psychometric properties of the Diabetes Management Experiences Questionnaire (DME‐Q). Adapted from the validated Glucose Monitoring Experiences Questionnaire, the DME‐Q captures satisfaction with diabetes management irrespective of treatment modalities. Methods: The DME‐Q was completed by adults with type 1 diabetes as part of a randomized controlled trial comparing hybrid closed loop (HCL) to standard therapy. Most psychometric properties were examined with pre‐randomization data (n = 149); responsiveness was examined using baseline and 26‐week follow‐up data (n = 120). Results: Pre‐randomization, participants' mean age was 44 ± 12 years, 52% were women. HbA1c was 61 ± 11 mmol/mol (7.8 ± 1.0%), diabetes duration was 24 ± 12 years and 47% used an insulin pump prior to the trial. A forced three‐factor analysis revealed three expected domains, that is, 'Convenience', 'Effectiveness' and 'Intrusiveness', and a forced one‐factor solution was also satisfactory. Internal consistency reliability was strong for the three subscales (α range = 0.74–0.84) and 'Total satisfaction' (α = 0.85). Convergent validity was demonstrated with moderate correlations between DME‐Q 'Total satisfaction' and diabetes distress (PAID: rs = −0.57) and treatment satisfaction (DTSQ; rs = 0.58). Divergent validity was demonstrated with a weak correlation with prospective/retrospective memory (PRMQ: rs = −0.16 and − 0.13 respectively). Responsiveness was demonstrated, as participants randomized to HCL had higher 'Effectiveness' and 'Total satisfaction' scores than those randomized to standard therapy. Conclusions: The 22‐item DME‐Q is a brief, acceptable, reliable measure with satisfactory structural and construct validity, which is responsive to intervention. The DME‐Q is likely to be useful for evaluation of new pharmaceutical agents and technologies in research and clinical settings. [ABSTRACT FROM AUTHOR]

Context: Many adrenal adenomas exhibit mild autonomous cortisol secretion (MACS). Although MACS is associated with increased cardiovascular mortality, the underlying mechanisms are not fully defined. Objective: To investigate mechanisms that may link MACS and cardiovascular mortality in adults with adrenal adenoma. Design: Cross-sectional study. Patients: Twenty adults with adrenal adenoma and MACS and 20 controls with nonfunctioning adrenal adenoma. Methods: Reactive hyperemia index (RHI) was measured by peripheral artery tonometry and 24-hour ambulatory blood pressure monitoring (24h AMBP) was performed. Indices of insulin secretion and sensitivity were estimated by measuring glucose and insulin fasting and following a mixed meal. Main outcome measure: The primary outcome was the difference in RHI between participants with MACS vs nonfunctioning adrenal adenoma. Results: The average cortisol after 1-mg dexamethasone and urinary free cortisol were higher in patients with MACS. There was no significant difference in fasting RHI (2.0 [interquartile range (IQR) 1.6-2.4] vs 2.0 [IQR 1.7-2.2, P = .72), but postprandial RHI was higher in patients with MACS (2.2 [1.8-2.7] vs 1.8 [1.5-2.2], P = .04). 24-hour ambulatory blood pressure monitoring and Matsuda index were not significantly different in the groups. Fasting glucose and glucose area under the curve after the mixed meal were higher and insulinogenic index was lower in participants with MACS. Conclusion: Adults with adrenal adenoma and MACS do not have fasting endothelial dysfunction and postprandial endothelial function may be better. These patients have fasting and postprandial hyperglycemia with lower insulin secretion, which may underlie the association between MACS and increased cardiovascular mortality. [ABSTRACT FROM AUTHOR]

The fact that growth hormone (GH) plays an important role in health after the cessation of growth requiring replacement therapy in adult life has only been recognised in the last three decades. This has only been made possible by recombinant technology providing GH supplies required to undertake investigations in the physiology of GH action and the benefits of replacement therapy in patients identified by rigorously validated diagnostic tests for GH deficiency (GHD). Human studies have revealed important regulatory roles in substrate metabolism, sodium homeostasis, body composition, and physical function. GH-induced anabolism is achieved by stimulating amino acid incorporation into protein while reducing oxidative loss simultaneously enhancing lipid utilisation by stimulating fatty acid oxidation and reducing lipid storage. Sodium and fluid retention are enhanced by activating the renin–angiotensin system and distal renal tubular reabsorption. GH stimulates the aerobic and anaerobic energy systems that underpin muscle and cardiovascular function. These pleiotropic actions explain the clinical picture of increased adiposity, reduced lean mass, and impaired physical and psychological function in the GHD adult, all of which are reversed when GH is replaced. Women require a greater replacement dose of GH than men. This is because androgens enhance while oestrogens attenuate GH action. The oestrogen effect is route-dependent, occurring with oral delivery blunting the liver-mediated actions of GH by directly inhibiting GH receptor signalling, global experience spanning over 30 years has attested to the safety, efficacy, and benefits of replacement therapy for adults with GHD. [ABSTRACT FROM AUTHOR]

Adrenal adenomas are incidentally identified in up to 5% of computer tomography scans performed for unrelated indications. A proportion of these adrenal incidentalomas are found to autonomously secrete cortisol based on definitions in current guidelines. Epidemiological studies suggest that chronic exposure to mild glucocorticoid excess from adrenal incidentalomas is associated with significantly increased cardiometabolic risk. However, current management guidelines adopt a conservative approach as no large prospective randomized studies have demonstrated that these patients benefit from surgery. This narrative review examines the epidemiological and mechanistic studies related to three common clinical settings of mild glucocorticoid excess to gain further insight into the potential benefits of treating patients with adrenal incidentaloma and possible autonomous cortisol secretion. [ABSTRACT FROM AUTHOR]

How protein metabolism is perturbed during chronic glucocorticoid excess is poorly understood. The aims were to investigate the impact of chronic glucocorticoid excess and restoration of eucortisolemia in Cushing's syndrome (CS) on whole body protein metabolism. Eighteen subjects with CS and 18 normal subjects (NS) underwent assessment of body composition using DEXA and whole body protein turnover with a 3-h constant infusion of L-[[sup.13]C]leucine, allowing calculation of rates of leucine appearance (leucine [R.sub.a]), leucine oxidation ([L.sub.ox]), and leucine incorporation into protein (LIP). Ten subjects with CS were restudied after restoration of eucortisolemia. Percentage FM was greater (43.9 [+ or -] 1.6 vs. 33.8 [+ or -] 2.4%, P = 0.002) and LBM lower (52.7 [+ or -] 1.6 vs. 62.1 [+ or -] 2.3%, P = 0.002) in CS. LBM was significantly correlated ([r.sup.2] > 0.44, P < 0.005) to leuceine [R.sub.a], [L.sub.ox], and LIP in both groups. After correcting for LBM, leucine [R.sub.a] (133 [+ or -] 5 vs. 116 [+ or -] 5 [micro]mol/min, P = 0.02) and [L.sub.ox] (29 [+ or -] 1 vs. 24 [+ or -] 1 [micro]mol/min, P = 0.01) were greater in CS. FM significantly correlated ([r.sup.2] = 0.23, P < 0.05) with leucine [R.sub.a] and LIP, but not [L.sub.ox] in CS. In multiple regression, LBM was an independent determinant of all three indexes of leucine turnover, FM of leucine [R.sub.a], and LIP and CS of [L.sub.ox]. Following restoration of eucortisolemia, [L.sub.ox] was reduced ([DELTA] - 7.5 [+ or -] 2.6 [micro]mol/min, P = 0.02) and LIP increased ([DELTA] + 15.2 [+ or -] 6.2 [micro]mol/min, P = 0.04). In summary, whole body protein metabolism in CS is influenced by changes in body composition and glucocorticoid excess per se, which increases protein oxidation. Enhanced protein oxidation is a likely explanation for the reduced protein mass in CS. Successful treatment of CS reduces protein oxidation and increases protein synthesis to prevent ongoing protein loss. whole body leucine turnover; body composition; resting energy expenditure doi:10.1152/ajpendo.00524.2006